HYPOTHALAMIC-PITUITARY-THYROID AXIS IN CHRONIC-ALCOHOLISM .2. DEIODINASE ACTIVITIES AND THYROID-HORMONE CONCENTRATIONS IN BRAIN AND PERIPHERAL-TISSUES OF RATS CHRONICALLY EXPOSED TO ETHANOL

Thyroxine (T-4), triiodothyronine (T-3) concentrations, and the activi ties of the three deiodinase isoenzymes were measured in different bra in regions and peripheral tissues of rats. According to an animal mode l of alcohol addiction, ''behaviorally'' dependent rats having lost co ntrol over their intake of ethanol were compared with alcohol-naive co ntrols and ethanol experienced, but ''controlled'' consumers. The two kinds of alcohol-experienced rats were investigated either 24 hr or 3 months after ethanol withdrawal. The results of these four groups were compared with those of an ethanol-naive control group. During withdra wal, the activities of type II 5'-deiodinase (which catalyzes deiodina tion of T-4 and T-3 in the CNS) in both the ''behaviorally dependent'' rats and the ''controlled drinkers'' were significantly lower then in the alcohol-naive controls in the frontal cortex, parieto-occipital c ortex, hippocampus, and striatum, but not in the cerebellum or pituita ry. Probably as a result, the tissue concentrations of T-4 were higher in areas of the CNS in the groups exposed to alcohol. However, the T- 3 concentrations were normal. No relevant differences were seen betwee n the activities of type III 5-deiodinase (which catalyzes the further deiodination of T-3) observed in these groups. After 3 months of abst inence, the type II 5'-deiodinase activities had almost returned to no rmal in both ''controlled drinkers'' and ''behaviorally dependent'' an imals, whereas type III 5-deiodinase activity was inhibited, possibly to maintain physiological concentrations of T-3 during abstinence. Ind eed, the tissue levels of T-3 were normal in the areas of the CNS, and the T-4 levels were still elevated. However, the liver concentrations of T-3 and T-4 were significantly lower in the ''behaviorally depende nt'' animals than in the ''controlled'' drinkers after 3 months of abs tinence, whereas no differences were found between the T-4 and T-3 con centrations in the areas of the CNS investigated in the two groups exp osed to ethanol. These results suggest that chronic administration of ethanol affects intracellular thyroid hormone metabolism in both rat C NS and liver in a highly complex manner. No direct evidence of ethanol -induced enhancement of tissue uptake or concentrations was obtained. However, taking into account the numerous similarities between the cli nical picture of hyperthyroidism and the symptomatology of alcoholism, it may be hypothesised that ethanol may directly influence any step i n the as yet unknown biochemical cascade of thyroid hormone function.